Treatment response after relapse in a placebo-controlled maintenance trial in schizophrenia
Abstract
While placebo-controlled studies continue to be required by regulatory authorities for the licensing of new drugs for schizophrenia to demonstrate maintenance of effect, the long-term risks to participants are largely unknown. We compared the response to treatment with paliperidone palmitate before and after relapse in such a study. This was a post-hoc analysis of 97 patients with schizophrenia who relapsed while receiving placebo in a multinational relapse prevention clinical trial. Patients underwent an initial open-label treatment phase of 33 weeks (comprising a 9-week transition phase to switch patients to paliperidone palmitate, a 12-week flexible-dose phase and a 12-week fixed-dose phase); a double-blind phase of variable duration during which stabilized patients were randomized 1:1 to either continue paliperidone palmitate or receive placebo; and an optional 52-week open-label flexible-dose extension phase. There was a small but significant increase in PANSS total scores after eight months of treatment following relapse (56.7[12.68]) compared with prerelapse endpoint (54.5[11.74]) (p=0.026). Fourteen of 97 (14.4%) patients who had initially responded favorably to treatment met predefined nonresponse criteria in the postrelapse treatment phase, suggesting that treatment refractoriness may evolve in a subset of patients after relapse. However, relapses occurred in 18% of patients randomized to ongoing treatment in the double-blind phase, raising the possibility that treatment failure may also evolve in patients receiving continuous treatment. These findings may help inform decisions regarding the future of placebo-controlled trials in schizophrenia.
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Relapses may lead to reduced response to previously effective antipsychotics, potentially contributing to treatment resistance.
“Relapses may also lead to reduced response to previously effective antipsychotics, potentially contributing to treatment resistance [10–12].”
From Pharmacokinetic Characteristics of Long-Acting Injectable Antipsychotics for Schizophrenia: An Overview (2021) · cites this paper as [11]
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- Authors
- Emsley, R., Nuamah, I., Hough, D., & Gopal, S.
- Affiliations
- Stellenbosch University (ZA)
- Janssen Research & Development (United States) (US)
- Corresponding author
- Emsley, Robin
- Venue
- Schizophrenia Research
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 138
- Issue
- 1
- Pages
- 29-34
- ISSN
- 0920-9964 (ISSN-L)
- OpenAlex
- W2132729780
- Cited by
- 110
- References
- 40
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 16 · 2020: 8 · 2019: 10 · 2018: 6 · 2017: 5 · 2016: 7 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 2
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Schizophrenia Research (publishedVersion)
- PubMed (publishedVersion)
- SUNScholar (Stellenbosch University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- schizophrenia, relapse
- MeSH terms
- Paliperidone Palmitate, Adult, Clinical Trials as Topic, Female, Humans, Isoxazoles, Male, Middle Aged, Palmitates, Placebos, Recurrence, Schizophrenia, Antipsychotic Agents, Treatment Outcome, Treatment Failure
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